In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

Hoves, Sabine; Aigner, Michael; Pfeiffer, Christian; Laumer, Monika; Obermann, Ellen C.; Mackensen, Andréas

doi:10.1038/leu.2008.391

Cited by 18 publications

(11 citation statements)

References 39 publications

(42 reference statements)

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“…Vasuri et al (2010) have reported strong expression of LMP2 and LMP7 in fetal hematopoietic elements and suggested a possible role of immunoproteasome during the hepatic phase of human hematopoiesis. Hoves et al (2009) the majority of AML blasts (70-90%) with the exception of LMP7 which was positive in the majority (66%) of all AML samples. It can be concluded that downregulation of APM components may play a role in the failure of immuno-surveillance and may therefore contribute to relapse in acute leukemia.…”

Section: Discussionmentioning

confidence: 99%

“…Defects in APM components have been correlated with progression and survival in various human tumors (Meissner et al, 2005;Seliger et al, 2006;Mehta et al, 2007). A tissue microarray analysis indicated significant downregulation of APM components in acute myeloid leukaemic (AML) blasts and it was concluded that multiple deficiencies in APM expression play role in the failure of immunosurveillance and may therefore contribute to relapse in the disease (Hoves et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Association of an LMP2 Polymorphism with Acute Myeloid Leukemia and Multiple Myeloma

Özbas‐Gerçeker

Bozman²,

Kok³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Hematological malignancies (HM) are a group of neoplasms derived from the cells of the bone marrow and lymphatic system. Genetic factors leading to susceptibility to HM have been investigated for years but little is known yet. Low molecular weight polypeptide (LMP) 2 and LMP7 genes are important subunits of the immunoproteasome and play significant role in antigen presentation. The polymorphisms of LMP genes have been reported to be risk factors for various types of diseases. The aim of this study was to investigate the association of LMP2 and LMP7 polymorphisms with the occurrence of particular types of HM. A total of 132 patients with HM and 130 control subjects were investigated. No significant difference was obtained in the distribution of genotype and allele frequencies of LMP7 gene in HM patients and the control group. On the other hand, the prevalence of LMP2-AA genotype was found to be higher in acute myeolid leukemia (AML) patients while it was significantly lower in multiple myeloma (MM) cases than in the control subjects. Our results suggested that LMP7 could not be a risk factor for susceptibility to HM, whereas LMP2 polymorphisms could play a role in the development of AML and MM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of an LMP2 Polymorphism with Acute Myeloid Leukemia and Multiple Myeloma

Özbas‐Gerçeker

Bozman²,

Kok³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Moreover, impaired MHC class I-mediated antigen presentation has been recognized as a major immune evasion mechanism in various cancers [8, 9, 53–56]. The high frequency of loss of MHC class I has been reported in 92% of cervical cancers [57], 71% of breast cancers [58], 64% of non-small cell lung cancers [59], 67% of esophageal squamous cell carcinomas [60] and in others [61–65]. Various molecular mechanisms reported account for the loss of MHC class I, including loss of heterozygosity in HLA-A, -B, -C or B2M genes [66, 67]; somatic mutations in HLA, B2M, TAP1/2 or LMPs [67–71]; HLA gene methylation [72, 73]; post-translational changes in TAP1 [71]; and defective JAK-STAT pathway at the IFN-γ receptor signaling [74].…”

Section: Nlrc5-targeted Immune Evasion In Cancermentioning

confidence: 99%

NLRC5/CITA: A Key Player in Cancer Immune Surveillance

et al. 2017

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Cancer cells need to escape immune surveillance for successful tumor growth. Loss of MHC class I has been described as a major immune evasion strategy in many cancers. MHC class I transactivator (CITA), NLRC5, has found to be a key transcription coactivator of MHC class I genes. Recent genetic studies revealed that NLRC5 is a major target for cancer immune evasion mechanism. The reduced expression or activity of NLRC5 caused by promoter methylation, copy number loss, or somatic mutations is associated with defective MHC class I expression, impaired cytotoxic T cell activation and poor patient prognosis. Here we review the role of NLRC5 in cancer immune evasion and the future prospects for cancer research.

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“…The MHC class I antigen processing and presentation pathway is critical for host tumor surveillance. Expressions of APM components have been found to be undetectable or lost in many tumor types [12,13,36]. Restoring TAP1 expression by introducing exogenous TAP1 could correct the HLA Class I antigen deficiency, which may result in recognition of these antigen-presenting cells by primed CTL [22,24].…”

Section: Discussionmentioning

confidence: 97%

“…In addition, HLA class I molecules are essential for recognition and eradication of tumor cells by primed CTL. In the HLA class I pathway, having intact antigen-processing machinery (APM) ensures the appropriate processing and presentation of antigens produced by tumor cells [13]. The APM includes the following molecules: transporters associated with antigen processing 1 and 2 (TAP1 and TAP2), low-molecular-weight proteins 2 and 7 (LMP2 and LMP7), and tapasin.…”

Section: Introductionmentioning

confidence: 99%

HMME-based PDT restores expression and function of transporter associated with antigen processing 1 (TAP1) and surface presentation of MHC class I antigen in human glioma

Zhang

et al. 2011

J Neurooncol

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Numerous studies have established that photodynamic therapy (PDT) can trigger tumor-specific immunity and cancer cell immunogenicity, both of which play a critical role in the long-term control of oncogenesis; however, the underlying mechanisms are largely unexplained. Deficiency of the transporter associated with antigen processing 1 (TAP1) has been observed in a variety of tumors, and the question has been raised whether the restoration of TAP1 could facilitate the activation of antitumor immunity. To elucidate the mechanisms underlying PDT-induced immunopotentiation, we examined the hypothesis that upregulating TAP1 via PDT may contribute to enhancement of antitumor immunity and cancer cell immunogenicity. In this study, we investigated the effects of PDT on the expression and function of TAP1 in glioma cells. We found that HMME-based PDT restored TAP1 expression in a rapid and transient manner. Furthermore, the newly synthesized TAP1 protein was capable of potentiating the activity of transporting antigen peptides. As a result, restoration of the expression and function of TAP1 translated into augmenting the presentation of surface MHC class I molecules. Overall, our data indicate that PDT enables glioma cells to recover both the expression of functional TAP1 and the presentation of surface MHC class I antigens, which are processes that may enhance antitumor immunity after PDT. These findings may have implications for PDT and provide new insights into the mechanisms underlying PDT-induced immunopotentiation.

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In situ analysis of the antigen-processing machinery in acute myeloid leukaemic blasts by tissue microarray

Cited by 18 publications

References 39 publications

Association of an LMP2 Polymorphism with Acute Myeloid Leukemia and Multiple Myeloma

Association of an LMP2 Polymorphism with Acute Myeloid Leukemia and Multiple Myeloma

NLRC5/CITA: A Key Player in Cancer Immune Surveillance

HMME-based PDT restores expression and function of transporter associated with antigen processing 1 (TAP1) and surface presentation of MHC class I antigen in human glioma

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